Clinical application of vancomycin TDM in ventilated patients with gastrointestinal cancer: a propensity-matched analysis.

BACKGROUND: Therapeutic drug monitoring (TDM) of vancomycin is widely recommended for clinical treatment. Due to the complexity of 24-h area under the curve (AUC) guided vancomycin monitoring in clinical practice, the vancomycin trough level remains the most common and practical method. The purpose of this study was designed to investigate the differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods, and further explore the clinical application of trough-guided vancomycin monitoring in patients with gastrointestinal cancer requiring mechanical ventilation. METHODS: We included a total of 78 gastrointestinal cancer patients who required mechanical ventilation due to various diseases. All patients included in this study were aged 18 years or older and were treated with intravenous vancomycin therapy for more than 2 days due to documented or suspected Gram-positive bacterial infections, and have at least one available vancomycin plasma concentration. First, we compared the safety and efficacies of vancomycin TDM based on different monitoring methods as trough-guided monitoring or AUC-guided monitoring. Then, based on whether the initial vancomycin concentration achieving the target trough concentration (less than 48 h), patients were divided into early and delayed groups, and the clinical factors were compared between them. The primary endpoints include the incidence of new-onset acute kidney injury (AKI) or renal replacement therapy (RRT), clinical success rate and 28-day all-cause mortality. Finally, the overall relationship between trough concentration and potential covariates is screened by univariate and multivariate analysis to explore potential information covariates. RESULTS: The research revealed that patients with gastrointestinal cancer exhibited significantly lower initial vancomycin trough concentrations (median [interquartile range (IQR)]: 6.90[5.28-11.20] mg/L). And there were no statistically significant differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods for the primary endpoint. Moreover, base on trough-guided vancomycin monitoring, the early group demonstrated a notably shorter duration of mechanical ventilation compared with the delayed group (χ2 = 4.532; p < 0.05; Fig. 2E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2 = 6.607; p < 0.05; Fig. 2F) and duration of vasoactive agent (χ2 = 6.106; p < 0.05; Fig. 2D) were significantly shorter in the early group compared with delayed group. Multivariate regression analysis revealed that Cystatin C (Cys-C) was the most important variable for vancomycin target trough achievement (odds ratio, 5.274; 95% CI, 1.780 to 15.627; p = 0.003). CONCLUSIONS: Trough-guided vancomycin monitoring is a simple and effective marker of TDM for ventilated patients with gastrointestinal cancer. Timely achievement of target trough concentrations for vancomycin can improve partial clinical outcomes in Gram-positive bacterial infections. Cys-C level is a potentially valuable parameter for predicting the vancomycin concentration.

Characteristics of four commonly used self-expanding biliary stents: an in vitro study.

BACKGROUND: Knowledge of the characteristics of self-expanding metal stents (SEMSs) is essential during selection process to ensure the best therapeutic outcomes for patients with malignant biliary obstruction. The aim of this study was to evaluate the characteristics of four commonly used SEMSs. METHODS: This in vitro study analyzed the radial force (RF), crush resistance (CR), axial force (AF), conformability, surface quality, foreshortening, and radiopacity of the following SEMSs: uncovered Wallflex™, EGIS single bare, Zilver 635®, and E-Luminexx™. Two samples of each SEMS type were included in this study, all having identical specifications with a diameter of 10 mm and a length of 6 cm. One sample from each type was analyzed for surface quality, followed by CR, conformability, and foreshortening. The other sample was analyzed for radiopacity, followed by RF and AF. RESULTS: The uncovered Wallflex™ exhibited low RF, high CR, high AF, good conformability, poor surface quality, high foreshortening, and good radiopacity. The EGIS single bare demonstrated high RF, high CR, low AF, moderate conformability, good surface quality, high foreshortening, and poor radiopacity. The Zilver 635® displayed moderate RF, low CR, low AF, moderate conformability, moderate surface quality, no foreshortening, and good radiopacity. The E-Luminexx™ showed high RF, moderate CR, high AF, poor conformability, poor surface quality, no foreshortening, and good radiopacity. CONCLUSIONS: There was considerable variation in the characteristics among the four evaluated SEMSs. These characteristics should be carefully considered during selection to ensure optimal therapeutic outcomes for patients. RELEVANCE STATEMENT: The selection of self-expanding metal stents for treating malignant biliary obstruction requires careful consideration of various characteristics, including their radial force, crush resistance, axial force, conformability, surface quality, foreshortening, and radiopacity. KEY POINTS: • The characteristics of self-expanding metal stents (SEMSs) can vary considerably. • Specific situations may warrant the use of SEMSs with particular characteristics over others. • Characteristics of SEMSs must be considered during selection for optimal outcomes.

Local hyperthermia mediated by gold nanoparticle-integrated silicone-covered stent: feasibility and tissue response in a rat esophageal model.

BACKGROUND: To assess the feasibility and tissue response of using a gold nanoparticle (AuNP)-integrated silicone-covered self-expandable metal stent (SEMS) for local hyperthermia in a rat esophageal model. METHODS: The study involved 42 Sprague-Dawley rats. Initially, 6 animals were subjected to near-infrared (NIR) laser irradiation (power output from 0.2 to 2.4 W) to assess the in vitro heating characteristics of the AuNP-integrated SEMS immediately after its placement. The surface temperature of the stented esophagus was then measured using an infrared thermal camera before euthanizing the animals. Subsequently, the remaining 36 animals were randomly divided into 4 groups of 9 each. Groups A and B received AuNP-integrated SEMS, while groups C and D received conventional SEMS. On day 14, groups A and C underwent NIR laser irradiation at a power output of 1.6 W for 2 min. By days 15 (3 animals per group) or 28 (6 animals per group), all groups were euthanized for gross, histological, and immunohistochemical analysis. RESULTS: Under NIR laser irradiation, the surface temperature of the stented esophagus quickly increased to a steady-state level. The surface temperature of the stented esophagus increased proportionally with power outputs, being 47.3 ± 1.4 °C (mean ± standard deviation) at 1.6 W. Only group A attained full circumferential heating through all layers, from the epithelium to the muscularis propria, demonstrating marked apoptosis in these layers without noticeable necroptosis. CONCLUSIONS: Local hyperthermia using the AuNP-integrated silicone-covered SEMS was feasible and induced cell death through apoptosis in a rat esophageal model. RELEVANCE STATEMENT: A gold nanoparticle-integrated silicone-covered self-expanding metal stent has been developed to mediate local hyperthermia. This approach holds potential for irreversibly damaging cancer cells, improving the sensitivity of cancer cells to therapies, and triggering systemic anticancer immune responses. KEY POINTS: • A gold nanoparticle-integrated silicone-covered self-expanding metal stent was placed in the rat esophagus. • Upon near-infrared laser irradiation, this stent quickly increased the temperature of the stented esophagus. • Local hyperthermia using this stent was feasible and resulted in cell death through apoptosis.

Experimental study on the significance of pressure relief effect and crack extension law under uniaxial compression of rock-like materials containing drill holes.

The drilling pressure relief technology is an effective way to reduce the accumulation of elastic energy in the tunnel envelope, which can reduce the risk of regional ground pressure occurrence. However, there is a lack of theoretical guidance on which drilling parameter has the greatest degree of influence on the effectiveness of pressure relief. The uniaxial compression tests were conducted to study the relationships between drilling parameters (the diameter, depth, and spacing) and the mechanical properties and deformation modulus of specimens. The results show that: (1) The drilling diameter (DDR) and drilling depth (DDH) of single-hole specimens negatively correlate with the peak-failure strength and deformation modulus, while the drilling spacing (DS) of double-hole specimens positively correlates with the peak-failure strength and deformation modulus. It shows that the borehole diameter has a more significant effect on the decompression effect. (2) With the help of the Grey Relational Analysis, the factors affecting the peak-failure strength and deformation modulus of the drilled specimens were ranked in significance. From the largest to the smallest, they are DDR, followed by DDH and DS. (3) The role of the pressure relief mechanism is to transfer the high stress in the shallow part of the roadway to the deep part, reduce the peak strength of destruction and deformation modulus of the peripheral rock in the drilled section, so that the characteristics of the mechanical behavior of the rock are significantly weakened, and the range of the area of the drilled hole decompression is enlarged. During the loading of the borehole, the borehole stress field dominates in the early stage, and cracking starts near the borehole along the direction perpendicular to the direction of maximum principal stress (horizontal direction). In the later stage, the maximum principal stress field dominates and vertical cracks with large widths appear. During crack expansion, the plastic energy dissipation effect is enhanced and the deep impact conduction path is weakened, thus protecting the roadway. This study determined the significance of the pressure relief effect of different drilling parameters, which can guide reasonable modifications of drilling parameters in the field.

Efficacy and prognostic factors of COVID-19 vaccine in patients with hepatocellular carcinoma: Analysis of data from a prospective cohort study.

BACKGROUND: The efficacy of coronavirus disease 2019 (COVID-19) vaccines in preventing SARS-CoV-2 infection in patients with hepatocellular carcinoma (HCC) is not clear. METHODS: From January 2022 to October 2022, patients diagnosed with HCC in a prospective, multicenter, observational cohort were analyzed. RESULTS: One hundred and forty-one patients with (n = 107) or without COVID-19 vaccination (n = 34) were included. The number of patients with severe or very severe infection was relatively lower in the vaccinated group (3.7% vs. 11.8%, p = 0.096). Median infection-free survival in the vaccinated group (14.0 vs. 8.3 months, p = 0.010) was significantly longer than that in the unvaccinated group. COVID-19 vaccination (hazard ratio (HR) HR = 0.47), European Cooperative Oncology Group performance score = 0 (HR = 2.06), and extrahepatic spread (HR = 0.28) were found to be the independent predictive factors for infection-free survival. CONCLUSION: COVID-19 vaccines could effectively reduce the SARS-Cov-2 infection in patients with HCC.

A Novel Rat Model to Simulate the Benign Esophageal Stricture Induced by Endoscopic Submucosal Dissection.

Objective: This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD). Materials and Methods: Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery. Results: Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group. Conclusion: A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.